Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects.

The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines.

Error-free and error-prone DNA repair gene expression data through reprogramming and passage in human iPS cells.

We recently found that DNA repair-related gene expression could be altered by reprogramming as well as the increased expression of genes that accurately convey genomic information, such as homologous recombination (HR) and mismatch repair (MMR), and the decreased expression of error-prone translesion synthesis (TLS) polymerase. Here, we confirmed this change in expression in another cell-line and found that such alteration was maintained by overlapping passages as well as OCT3/4 and NANOG. Our findings suggest that changes in the expression of DNA repair-related genes associated with reprogramming and their maintenance can be novel indicators of the quality control of the cells exhibiting pluripotency.

Generation of targeted homozygosity in the genome of human induced pluripotent stem cells.

When loss of heterozygosity (LOH) is correlated with loss or gain of a disease phenotype, it is often necessary to identify which gene or genes are involved. Here, we developed a region-specific LOH-inducing system based on mitotic crossover in human induced pluripotent stem cells (hiPSCs). We first tested our system on chromosome 19.

Increased error-free DNA repair gene expression through reprogramming in human iPS cells.

Introduction: Many studies have reported that human-induced pluripotent stem (hiPS)/embryonic stem (hES) cells have an exceptional ability to repair damaged DNA. Moreover, unlike differentiated cells, hES cells have features and mechanisms such as apoptosis-prone mitochondria, which prevent any changes in genetic information caused by DNA damage to be transmitted to their descendants. Type-A (dark) spermatogonia and cancer stem cells are thought to be dormant.

Removal of reprogramming transgenes improves the tissue reconstitution potential of keratinocytes generated from human induced pluripotent stem cells.

Human induced pluripotent stem cell (hiPSC) lines have a great potential for therapeutics because customized cells and organs can be induced from such cells. Assessment of the residual reprogramming factors after the generation of hiPSC lines is required, but an ideal system has been lacking. Here, we generated hiPSC lines from normal human dermal fibroblasts with piggyBac transposon bearing reprogramming transgenes followed by removal of the transposon by the transposase.

Induction of pluripotent stem cells from human third molar mesenchymal stromal cells.

The expression of four transcription factors (OCT3/4, SOX2, KLF4, and MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. We generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without MYC, which is considered as oncogene. Interestingly, some of the clonally expanded MSCs could be used for iPS cell generation with 30-100-fold higher efficiency when compared with that of other clonally expanded MSCs and human dermal fibroblasts.

Green fluorescent protein as a marker in transgenic mice.

Green fluorescent protein (GFP) found in Aequorea victoria absorbs blue light and emits green fluorescence without exogenous substrates or co-factors. We studied the possibility of using the GFP as a marker in mammals. Transgenic mice were produced using the GFP coding sequence, ligated with the chicken beta-actin promoter.